U.S. patent application number 09/755607 was filed with the patent office on 2003-06-05 for skin product having micro-spheres, and processes for the production thereof.
Invention is credited to Bettle, Griscom, Coury, William S., Pettersson, Berno I..
Application Number | 20030104018 09/755607 |
Document ID | / |
Family ID | 25039844 |
Filed Date | 2003-06-05 |
United States Patent
Application |
20030104018 |
Kind Code |
A1 |
Bettle, Griscom ; et
al. |
June 5, 2003 |
Skin product having micro-spheres, and processes for the production
thereof
Abstract
Skin and/or wound and burn care compositions and/or phase stable
emulsions comprising one or more of the following; organic base
salts of fatty acids, fatty esters, fatty alcohols, non-ionic and
quaternary ammonium surfactants, and other highly polar compounds,
a liquid carrier, and optionally one or more active agents. The
compositions and/or phase stable emulsions contain fatty
microspheres. The compositions that are especially adapted to
topically deliver active and/or medicinal agents to the surface of
the skin, burns, skin lesions, warts, and ulcers, and methods for
preparing such compositions.
Inventors: |
Bettle, Griscom; (Sarasota,
FL) ; Pettersson, Berno I.; (Perry, GA) ;
Coury, William S.; (Sarasota, FL) |
Correspondence
Address: |
NEEDLE & ROSENBERG P C
127 PEACHTREE STREET N E
ATLANTA
GA
30303-1811
US
|
Family ID: |
25039844 |
Appl. No.: |
09/755607 |
Filed: |
January 5, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09755607 |
Jan 5, 2001 |
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09331817 |
Jun 25, 1999 |
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09331817 |
Jun 25, 1999 |
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PCT/US97/24220 |
Dec 31, 1997 |
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60033796 |
Dec 31, 1996 |
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Current U.S.
Class: |
424/401 |
Current CPC
Class: |
A61K 8/39 20130101; A61K
8/81 20130101; A61K 9/7015 20130101; A61K 8/416 20130101; A61K 8/92
20130101; A61K 8/375 20130101; A61K 2800/94 20130101; A61K 9/113
20130101; A61Q 19/00 20130101; A61K 8/988 20130101; A61K 8/342
20130101; A61K 8/927 20130101; A61K 8/36 20130101 |
Class at
Publication: |
424/401 |
International
Class: |
A61K 007/00 |
Claims
1. A method of treating or preventing ailments of the skin,
comprising applying to the surface of animal skin or tissue an
effective amount of a composition capable of forming a film that
ionically bonds to the skin or tissue comprising the residue of: a.
one or more active agents; b. a nonionic or substantially nonionic
first film forming component; c. one or more cationic surfactants
comprising one or more fatty moieties that are soluble in the first
film forming component; and d. a liquid carrier.
2. The method of claim 1 wherein the first film forming component
comprises the residue of: a. one or more waxes; b. propolis; c. a
fatty acid comprising from about 10 to about 26 carbon atoms; and
d. a fatty alcohol comprising from about 10 to about 26 carbon
atoms:
3. The method of claim 2 wherein the one or more waxes comprise
natural or synthetic bees wax.
4. The method of claim 2 wherein the first film forming component
further comprises a monoester monoglyceride.
5. The method of claim 1 wherein the cationic surfactant comprises
an ammonium compound that is substituted with one or more lower
alkyl moieties, and one or more fatty moieties comprising from 16
to 22 carbon atoms.
6. The method of claim 1 wherein the cationic surfactant comprises
the solution or reaction residue of dimethyl distearyl ammonium
chloride.
7. The method of claim 1 wherein the composition further comprises
a partitioning agent.
8. The method of claim 7 wherein the partitioning agent is a
nonionic polyethoxylated fatty ether or alcohol.
9. The method of claim 1 wherein the composition further comprises
from about 0.1 to about 3.0 wt. % polyethyloxylated ether or
alcohol.
10. The method of claim 1 wherein the first film forming component
comprises an adduct of a nitrogenous organic base and a fatty
acid.
11. The method of claim 10, wherein the nitrogenous organic base is
triethanolamine.
12. The method of claim 10 wherein the fatty acid is stearic acid,
conjugated linolenic acid, alpha linolenic acid, gamma linolenic
acid, dihomogamma linolenic acid, docosahexaenoic acid, or
eicosapentaenoic acid.
13. The method of claim 1, wherein the composition comprises a
phase stable emulsion comprising the residue of: a. one or more
quaternary ammonium compounds; b. one or more surfactants; c. one
or more fatty esters; d. one or more fatty alcohols; and e.
optionally one or more highly polar compounds; wherein the ratio of
the sum of the moles of quaternary ammonium compounds, surfactants,
and highly polar compounds to the sum of the moles of fatty esters
and alcohols is from about 0.8 to about 1.2.
14. The method of claim 1, wherein the composition is in the form
of an emulsion for delivering one or more medicinal active agents
to the surface of the skin, comprising a fatty phase, wherein the
fatty phase comprises one or more fatty acids and wherein the one
or more active agents comprise one or more medicinally active
agents.
15. The composition of claim 14 wherein the fatty phase further
comprises one or more glycerides, and optionally comprises other
fatty components, wherein the molar ratio of the one or more fatty
acids to the one or more glycerides and other fatty components is
from about 0.5 to about 5.5.
16. The composition of claim 15 wherein the ratio is about 2.0.
17. The composition of claim 3 wherein the first film component is
modified with a stearic acid/nitrogenous base adduct.
18. The method of claim 1 wherein the composition has a pH of from
about 6.5 to about 8.5.
19. The method of claim 1 wherein the composition has a pH of from
about 7.1 to about 7.8.
20. The method of claim 1, wherein the active agent comprises from
about 0.01 weight % to about 3.0 weight percent of: a. an
alkylglycerol; b. an alkoxyglycerol; c. a polyunsaturated fatty
acid or oil; d. a fat soluble vitamin; e. a sulfur compound; f. a
mineral; g. an antioxidant; h. an amino acid; i. an energy
stimulator; j. steroidal or glycoprotein hormones; and/or k. other
healing agents selected from glycyrrhizic acid, ribonucleic acids,
aloe vera, allantoin, bioperine, berberine hydrochloride,
colostrum, dexpanthenol, glucosamine salts, inisitol, phytantriol,
pyrrolidine carboxylic acid, jojoba oil, symphytum officinal,
polysorbate 80, and vanilla extract.
Description
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of, and claims
priority to U.S. patent application Ser. No.09/331,817, filed Jun.
25, 1999, which was a U.S. National Phase filing under 37 U.S.C.
.sctn.371 based upon PCT Patent Application Serial No. PCT/US
97/24220, filed Dec. 31, 1997, which itself claimed priority to
U.S. Provisional Patent Application No. 60/033,796, filed Dec. 31,
1996, all of which applications are hereby incorporated by
reference, in their entireties.
FIELD OF THE INVENTION
[0002] This invention relates generally to skin products, and
particularly to emulsion-based skin products that can be applied to
the skin to provide continuing antimicrobial, antiviral,
antiseptic, and skin protecting or healing properties.
BACKGROUND OF THE INVENTION
[0003] People often use soaps and bactericides to remove and
exterminate undesirable contaminants such as dirt and bacteria from
the skin, especially the hands. These products are typically
applied to the skin while washing the hands under running water.
The products have a limited temporal effect, however, because they
are washed from the skin along with the dirt and bacteria during
the washing process. Conventional soaps and bactericides do not,
therefore, provide any lasting effect after they have been used.
However, in many occupations, such as the medical profession, it is
important to minimize and destroy harmful bacteria and viruses
immediately when they contact the skin. A skin product that
provided continued protection against contaminants with which the
skin comes into contact, after being applied to the skin, would
therefore be highly desirable. Such skin products should be
specifically formulated for the special demands of particular
applications.
[0004] In some applications, the need for rapid and anti-bacterial
and anti-viral activity is particularly important. For example,
surgeons and medical care practitioners require surgical scrub
products that sanitize their hands before surgery or like
procedures. FDA requires these products to have increasing efficacy
the longer they are used. That is, regulations require that
surgical scrub products improve their performance versus basic
soaps with repeated use.
[0005] Prior art surgical scrub products are harsh to the hands. A
typical surgical scrub product contains over 60% ethyl alcohol.
Those products are very effective at killing microorganisms, but
are equally effective at removing skin oils that make the skin soft
and substantially crack-free. When hands are cracked and sore, it
is more difficult to perform delicate surgery.
[0006] A product that matched the rapid anti-microbial behavior of
high-alcohol surgical scrubs, by use of formulations containing
aggressive anti-microbial agents, but which simultaneously coated
and protected the medical practitioner's hands would be especially
valuable.
[0007] Nevertheless, some skin is so damaged that aggressive
anti-microbial active ingredients are too irritating for use in
skin-care products. People who have developed a latex intolerance
are typical of this group, because allergic reactions to the
proteins or other irritants in latex products make their hands red
and sore to the point of bleeding. Such allergies can threaten the
careers of health care practitioners. If a skin-care product could
be formulated to form a layer that coated, soothed, and protected
the skin, yet could serve as a protective base layer for additional
layers containing anti-microbial active agents, health care
practitioners could protect themselves from harmful latex proteins,
yet protect their patients from pathogenic organisms.
[0008] A different special situation is presented for skin products
formulated for children younger than six years old. This population
has a well documented history of frequent infections, many of which
are transmitted via the hands. Children often have fingers and such
in their mouths, so special formulations are required to make a
safe and effective skin protectant product for children. A product
that could protect and simultaneously disinfect the hands of young
children, but be safe for them to occasionally ingest would improve
the health of this special population.
[0009] Another special situation is baby's bottoms. Babies are
prone to diaper rash and the like. A product that was gentle to
baby's skin, yet protected this tender skin from the bacteria of
feces and urine would be of particular advantage.
[0010] A skin-care product could also be adapted to topically
deliver active agents, such as drugs, continuously to wounded,
burned or ulcerated skin, or skin otherwise lacking in normal
integrity. For example, preparations for removing warts might
purposefully deliver toxic or irritating agents to selected areas
of wounded skin.
[0011] Yet another set of special situations is presented by
skin-care products formulated to topically deliver medicinally
active agents to burns and wounds. Optimum wound or burn care
products should (1) reduce inflammation by delivering
anti-inflammatory agents or biological precursors of
anti-inflammatory agents, (2) provide necessary nutrients and
building block precursors for the biologically produced
prostaglandin, leucotriene, and thromboxane compounds which
regulate inflammation and promote tissue healing or new skin growth
at a burn site which may have impaired blood supply, (3) promote
normal and/or healing microbial activity at the wound surface, yet
inhibit outside infections caused by external pathogenic bacteria
or viruses, and (4) optionally modify electrical charge density in
and around the wound so as to attract biologically provided
nutrients and building block precursors to the wound site, which
may have a deficient blood supply.
[0012] It would be especially desirable to formulate products for
the treatment of wounds, or thermal, chemical, or radiation burns,
to accomplish the above-described functional objectives. It would
be desirable to formulate a composition which promotes increased
levels of biosynthesized prostaglandin hormones such as PGE1, PGE3,
PGI2, which promote healing of damaged skin and tissue, and caused
decreased levels of prostaglandin PGE2, which produces undesirable
inflammatory responses at a wound site. It would also be desirable
to provide building block precursors of the hormones and other
necessary cellular components, such as vitamins, minerals, sulfur
compounds, saturated and unsaturated fatty acids,
neurotransmitters, anti-oxidants, and other compounds which promote
healing.
[0013] Prior art products provide anti-inflammatory compounds,
necessary nutrients, or antiseptic treatments followed by
non-sterile conditions, but none of the prior art teaches combining
all the above functions in one stable salve.
[0014] Of particular importance is the healing of wounds and
decubitus ulcers. A decubitous ulcer often begins as a bed shearing
force abrasion on an immobilized patient. Body pressure restricts
blood flow where the skin is in contact with the mattress. Necrosis
ensues within 30 minutes, and a Level 1 ulcer (bed sore) develops.
In more severe cases, the epidermal layer is disrupted (for example
by scratching) and bacteria enter the site. As the ulcer severity
increases, a deep sore opens up in a conical fashion. In a Level 4
decubitous ulcer, the bone is often visible.
[0015] Prior art treatments of Level 4 decubitous ulcers first
require sanitizing the wound to kill pathogenic micro-organisms, as
well as normally benign or beneficial micro flora. Medicines were
subsequently applied to the sanitary wound, or heavy debridement of
damaged tissue was repeatedly applied during prior art treatments.
Healing is problematic using such treatments, typically taking 6
months, and is successful less than half the time.
[0016] Improved compositions and methods for successfully treating
such ulcers within 1-2 months would substantially advance the art.
Indeed, improved compositions and methods for treating thermal
bums, radiation burns, surface wounds, deep wounds or ulcers,
warts, or diaper rash would substantially advance the medical
arts.
SUMMARY OF THE INVENTION
[0017] In accordance with the purpose(s) of this invention, as
embodied and broadly described herein, this invention, in one
aspect, relates to a method of treating or preventing ailments of
the skin, comprising applying to the surface of animal skin or
tissue an effective amount of a composition capable of forming a
film that ionically bonds to the skin or tissue comprising the
residue of: one or more active agents; a nonionic or substantially
nonionic first film forming component; one or more cationic
surfactants comprising one or more fatty moieties that are soluble
in the first film forming component; and a liquid carrier.
[0018] In another aspect the invention provides a method of
treating or preventing skin ailments comprising applying to the
surface of animal skin or tissue an effective amount of a
composition comprising the residue of: one or more quaternary
ammonium compounds; one or more surfactants; one or more fatty
esters; one or more fatty alcohols; and optionally one or more
highly polar compounds; wherein the ratio of the sum of the moles
of quaternary ammonium compounds, surfactants, and highly polar
compounds to the sum of the moles of fatty esters and alcohols is
from about 0.8 to about 1.2.
[0019] In Skin another aspect the invention provides a method of
treating or preventing skin ailments comprising applying to the
surface of tissue an effective amount of an emulsion composition
comprising the residue of a fatty phase, wherein: the fatty phase
comprises fatty acids, glycerides, and optionally other fatty
components, and the molar ratio of fatty acids to glycerides and
other fatty components is from about 0.5 to about 5.5.
[0020] Additional aspects and advantages of the invention will be
set forth in part in the description which follows, and in part
will be obvious from the description, or may be learned by practice
of the invention. The advantages of the invention will be realized
and attained by means of the elements and combinations particularly
pointed out in the appended claims. It is to be understood that
both the foregoing general description and the following detailed
description are exemplary and explanatory only and are not
restrictive of the invention, as claimed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] The accompanying drawing, which is incorporated in and
constitute a part of this specification, illustrates several
embodiments of the invention and together with the description,
serve to explain the principles of the invention.
[0022] FIG. 1 shows estimated volume of a patient's heel wound
versus time in days, wherein the wound was undergoing treatment
with the methods and compositions of the inventions, as disclosed
in Example 15.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0023] The present invention may be understood more readily by
reference to the following detailed description of preferred
embodiments of the invention and the Examples included therein.
Definitions and Use of Terms
[0024] Before the present compounds, compositions and methods are
disclosed and described, it is to be understood that this invention
is not limited to specific synthetic methods, or to specific
formulations or administration regimens, as such may, of course,
vary. It is also to be understood that the terminology used herein
is for the purpose of describing particular embodiments only and is
not intended to be limiting.
[0025] It must be noted that, as used in the specification and the
appended claims, the singular forms "a," "an" and "the" include
plural referents unless the context clearly dictates otherwise.
Thus, for example, reference to "a fatty ester" includes mixtures
of fatty esters, reference to "a liquid carrier" includes mixtures
of two or more such carriers, and the like.
[0026] It must also be noted that ingredients in the claimed
compositions can be referred to by more than one term, because of
the multiple functions that these ingredients perform. Thus,
ascorbyl palmitate acts as both a film forming stabilizer an
antioxidant, and vitamin; as do vitamin E and beta-carotene. Other
examples include EPA, CLA, DHA, and GLA which act as prostaglandin
stimulators, precursors to prostaglandins, and also stabilize the
final film, and facilitate the migration of medicinals through this
film, and thus to the skin; thereby enhancing the medicinal's
topical absorption. All of the previously mentioned are considered
fatty moieties of the final film. Another example is dimethyl
benzethonium chloride which acts as an antimicrobial, and also
enhances wound healing by modifying the charge at the wound site.
Another example is the adduct of a nitrogenous organic base and a
fatty acid, which can function both as an active agent and a
constituent of a film forming component. A final example is
arginine, and other amino acids which act as neurotransmitters
which stimulate the healing process and also are nutrients for use
at the wound site. Complexed minerals such as zinc sulphate and
copper curcumin act as antimicrobials, antifungals and also provide
nutrition to the wound for speedier healing.
[0027] Ranges are often expressed herein as from about one
particular value, and/or to about another particular value. When
such a range is expressed, it is to be understood that a more
preferred range is typically from the one particular value and/or
to the other particular value. Similarly, when values are expressed
as approximations, by use of the antecedent "about", will be
understood that the particular value is typically more preferred.
It will further be understood that the endpoints of each of the
ranges are significant both in relation to the other endpoint, and
independently of the other endpoint.
[0028] References in the specification and concluding claims to
parts by weight, of a particular element or component in a
composition or article, denotes the weight relationship between the
element or component and any other elements or components in the
composition or article for which a part by weight is expressed.
Thus, in a composition containing 2 parts by weight of component X
and 5 parts by weight component Y, X and Y are present at a weight
ratio of 2:5, and are present in such ratio regardless of whether
additional components are contained in the composition.
[0029] A residue of a chemical species, as used in the
specification and concluding claims, refers to the moiety that is
the resulting product of the chemical species in a particular
reaction scheme or subsequent formulation or chemical product,
regardless of whether the moiety is actually obtained from the
chemical species. Thus, an ethylene glycol residue in a polyester
refers to one or more --OCH.sub.2CH.sub.2O-- units in the
polyester, regardless of whether ethylene glycol was used to
prepare the polyester. Similarly, a residue of NaCl in solution,
under appropriate conditions, refers to the sodium anion and
chloride cation in solution.
[0030] The term "alkyl" as used herein refers to a branched or
unbranched saturated hydrocarbon group of 1 to 24 carbon atoms,
such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,
t-butyl, octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl
and the like. The term "lower alkyl" intends an alkyl group of from
one to six carbon atoms, preferably from one to four carbon atoms.
The term "cycloalkyl" intends a cyclic alkyl group of from three to
eight, preferably five or six carbon atoms.
[0031] The term "alkoxy" as used herein intends an alkyl group
bound through a single, terminal ether linkage; that is, an
"alkoxy" group may be defined as --OR where R is alkyl as defined
above. A "lower alkoxy" group intends an alkoxy group containing
from one to six, more preferably from one to four, carbon
atoms.
[0032] "Surface" of skin or tissue means the exposed area of skin
or tissue associated with a skin ailment, and thus can be below the
level of surrounding skin or tissue for deep wounds, ulcers, and
other ailments.
[0033] "Ailments of the skin" refers to skin disorders, and
include, for example, skin lesions, wounds, ulcers, bums, radiation
bums, diaper rash, blisters, acne, psoriasis, athlete's foot, and
warts.
[0034] The term "debridement" as used herein refers to a procedure
used in the treatment of bums, wounds, and ulcers, wherein the
burn, wound, or ulcer is subjected to vigorous mechanical or
pharmaceutical cleaning and/or sterilization, which can include
treatment with strong anti-microbial agents, or cutting away scabs
and dead or damaged tissue.
[0035] The term "bum" as used herein refers to tissue injury
resulting from excessive exposure to thermal, chemical, electrical,
or radioactive agents, or electromagnetic radiation.
[0036] "Optional" or "optionally" means that the subsequently
described event or circumstance may or may not occur, and that the
description includes instances where said event or circumstance
occurs and instances where it does not. For example, the phrase
"optionally substituted alkyl" means that the alkyl group may or
may not be substituted and that the description includes both
unsubstituted alkyl and alkyl where there is substitution.
[0037] By the term "effective amount" of a compound or property as
provided herein is meant such amount as is capable of performing
the function of the compound or property for which an effective
amount is expressed. As will be pointed out below, the exact amount
required will vary from process to process, depending on recognized
variables such as the compounds employed and the processing
conditions observed. Thus, it is not possible to specify an exact
"effective amount." However, an appropriate effective amount may be
determined by one of ordinary skill in the art using only routine
experimentation. Discussion
[0038] The invention is a creme or lotion composition that is
especially effective for treating or preventing skin related
ailments. The composition, when applied to the skin, provides a
protective film that promotes skin healing, and which can be
modified to topically deliver medicinal ingredients.
[0039] The composition has several novel aspects. Thus, in one
embodiment the invention provides a method of treating or
preventing ailments of the skin, comprising applying to the surface
of animal skin or tissue an effective amount of a composition
capable of forming a film that ionically bonds to the skin or
tissue comprising the residue of one or more active agents; a
nonionic or substantially nonionic first film forming component;
one or more cationic surfactants comprising one or more fatty
moieties that are soluble in the first film forming component; and
a liquid carrier.
[0040] In another aspect the invention provides a method of
treating or preventing skin ailments comprising applying to the
surface of animal skin or tissue an effective amount of a
composition comprising the residue of: one or more quaternary
ammonium compounds; one or more surfactants; one or more fatty
esters; one or more fatty alcohols; and optionally one or more
highly polar compounds; wherein the ratio of the sum of the moles
of quaternary ammonium compounds, surfactants, and highly polar
compounds to the sum of the moles of fatty esters and alcohols is
from about 0.8 to about 1.2.
[0041] In still another aspect the invention provides a method of
treating or preventing skin ailments comprising applying to the
surface of animal skin or tissue an effective amount of an emulsion
composition comprising the residue of a fatty phase, wherein: the
fatty phase comprises fatty acids, glycerides, and optionally other
fatty components, and the molar ratio of fatty acids to glycerides
and other fatty components is from about 0.5 to about 5.5. In
separate embodiments the molar ratio is from about 0.5 to about
3.5, and from greater than about 3.5 (i.e. above the range
encompassed by "about 3.5) to about 5.5.
[0042] From about 20 to about 40 parts by weight of one or more
active agents are typically present in the composition, although
from about 25 to about 35 parts by weight are preferred. The
ingredients that make up the first film forming component typically
comprise from about 1 to about 5 parts by weight of the total
composition, and preferably comprise from about 2 to about 4 parts
by weight. The composition typically comprises from about 0.2 to
about 5 parts by weight of cationic surfactant, and preferably
comprises from about 1 to about 3 parts by weight cationic
surfactant. From about 50 to about 80 parts by weight of the liquid
carrier are typically present in the composition, although from
about 60 to about 75 parts by weight are especially preferred.
[0043] The first film forming component is preferably insoluble in
the liquid carrier, and present in the composition as an emulsion.
When applied to the skin, the first film forming component forms a
hydrophobic film that covers the skin as the liquid carrier
evaporates. The hydrophobic film provides a suitable environment
for skin or tissue to heal. By bonding to the skin, the film can
also exclude water and harmful agents such as bacteria from the
surface of the skin.
[0044] The hydrophobic film may also act as a foundation for
imparting continuing properties to the skin. Antiviral and
antibacterial agents can be incorporated into the film, and thereby
provide residual protection against contaminants with which the
skin may come into contact. The hydrophobic film may also act as a
medium through which medicinal agents can migrate and be delivered
to the skin.
[0045] The hydrophobicity of the film can, of course, vary.
However, the film is preferably sufficiently hydrophobic, and the
film forming component sufficiently insoluble, to exclude water
(and dissolved active ingredients such as cleansers and
bactericides) from the surface of the skin as a film is formed on
the surface of the skin. The film that is formed is preferably
sufficiently impervious to water to minimize the incidence of water
(which can carry aggravating cleansers, bacteria and other
undesirable constituents) migrating through the film barrier.
[0046] Numerous formulations can be used as the first film forming
component. For example, the first film forming component can
include natural and synthetic polymers and waxes. For reasons that
will become apparent, preferred formulations solubilize fatty
moieties, and can selectively incorporate fatty moieties from ionic
compounds within their structure, while excluding other ionic
moieties from the compound, upon drying to form a film. Waxes,
which contain the esters of fatty acids and fatty alcohols (other
than glycerol), are especially suitable ingredients for the first
film forming component. Waxes that suitably interact with propolis
to impart the desired properties to the film are especially
preferred.
[0047] An especially suitable formulation for the first film
forming component comprises natural or synthetic bees wax;
propolis; one or more fatty acids; and one or more fatty alcohols.
Fatty refers generally to high molecular weight aryl, aliphatic,
cycloaliphatic, saturated or unsaturated, straight or branched
aliphatic compounds, preferably saturated and/or aliphatic and/or
straight The fatty acids and fatty alcohols typically comprise
greater than 10 or 12 carbon atoms, and/or less than 32, 26, or 18
carbon atoms. Thus, in one embodiment the fatty acid comprises from
about 10 to about 32 carbon atoms, and the fatty alcohol comprises
from about 10 to about 32 carbon atoms. In a preferred embodiment
the fatty acid comprises from about 12 to about 18 carbon atoms,
and the fatty alcohol comprises from about 12 to about 16 carbon
atoms. In an even more preferred embodiment, the fatty acid
comprises stearic acid, and the fatty alcohol comprises cetyl
alcohol or myristic alcohol. In addition to being an integral
element of the film, the fatty acid also preferably acts as a
surfactant after it has been neutralized. The fatty alcohol
preferably acts as an emulsifying agent. The alcohol can be
substituted with groups such as amides, alkyl, and allyl groups, to
tailor the alcohol to a specific set of requirements.
[0048] The bees wax is preferably natural, with crude, filtered
bees wax being especially preferred. The bees wax can, however, be
synthetic, or substituted with other natural waxes, as long as the
wax possesses a net positive charge and a chemical similarity to
natural bees wax, and interacts favorably with propolis. A
particularly suitable synthetic bees wax is the synthetic wax
manufactured by Alzo, Inc. of Sayreville, N.J., under the trade
name Waxenol-8-22 (arachidyl behenate).
[0049] The propolis may preferably comprise propolis wax or
propolis resin. The propolis may constitute a distinct ingredient
of the composition, or it may be added as part of another
ingredient such as the bees wax. The weight ratio of propolis to
bees wax preferably meets or exceeds the ratio at which propolis
and bees wax naturally occur (about 26:74).
[0050] The first filming component may optionally further comprise
the solution residue of a monoester monoglyceride. The acidic
residue of the monoester monoglyceride preferably comprises from
about 10 to about 18 carbon atoms, and most preferably comprises 12
carbon atoms. The monoglyceride may be unsaturated, and may have up
to three double bonds. Saturated monoglycerides are, however,
especially preferred. The monoglyceride may also be substituted
with, for example, one or more alkyl groups, especially the lower
alkyl groups. A particularly suitable monoglyceride is lauricidin
(distilled glyceryl monolaurate).
[0051] The first film forming component typically comprises from
about 1 to about 12 parts by weight monoester glyceride, from about
0.2 to about 3.0 parts by weight bees wax, from about 0.1 to about
1.5 parts by weight propolis, from about 1.5 to about 10 parts by
weight of one or more fatty acids, and from about 1 to about 8
parts by weight one or more fatty alcohols, independently or in
combination. The first film forming component preferably comprises
from about 2 to about 6 parts by weight monoester glyceride, from
about 0.5 to about 1.5 parts by weight bees wax, from about 0.2 to
about 0.6 parts by weight propolis, from about 3 to about 5 parts
by weight of one or more fatty acids, and from about 2 to about 4
parts by weight of one or more fatty alcohols, independently or in
combination.
[0052] The composition also preferably comprises a cationic
surfactant, preferably comprising one or more fatty moieties. It is
believed that the cationic surfactant binds ionically to the
anionic sites on the surface of the skin, and, because the fatty
moieties from the cationic surfactant are solubilized in the first
film, anchors the film to the skin. It is also believed that the
surfactant, by drawing the film toward the skin, helps to exclude
water from the surface of the skin. The surfactant is preferably
sufficiently cationic to achieve this anchoring function.
Similarly, the fatty moieties preferably are sufficiently soluble
and large, and have sufficient interaction with the film, to
achieve this anchoring function. For example, fatty moieties
comprising from about 12 to about 22 carbon atoms, and especially
fatty moieties comprising about 18 carbon atoms, are most
preferred.
[0053] The cationic surfactant preferably makes up at least 0.10
wt. % of the composition, and preferably comprises no more than
about 5.0 wt. % of the composition. Less cationic surfactant than
0.10 wt. % is not evenly distributed across the surface of the
film, and therefore is not as effective to evenly bond the film to
the skin, and uniformly exclude water from the surface of the skin.
More cationic surfactant exceeds current FDA regulations.
[0054] In one embodiment the fatty cationic surfactant of the
composition comprises an ammonium compound that is substituted with
at least one lower alkyl moiety. In another embodiment the ammonium
compound is substituted with from one to three lower alkyl
moieties, and one or more fatty moieties comprising from about 8 to
about 22 carbon atoms, preferably from about 16 to about 22 carbon
atoms. The fatty moiety can preferably be aryl, aliphatic,
cycloaliphatic, saturated or unsaturated, straight or branched. In
a more particular embodiment the cationic surfactant comprises the
solution residue of dimethyl distearyl ammonium chloride. A
dimethyl, ditallow ammonium chloride residue, with its broader
molecular weight distribution, is also preferred.
[0055] The liquid carrier for the composition can also vary.
Indeed, any carrier that does not substantially interfere with the
components or the function of the components, and which allows a
film to form and thereby exclude the carrier from the skin surface
as it evaporates, is suitable. Exemplary carriers include water,
and lower molecular weight alcohols such as ethanol, isopropyl
alcohol, sec-butyl alcohol, glycerin, and propylene glycol,
although water is generally preferred for the particular
ingredients described in this document.
[0056] The composition may comprise one or more active agents,
which are chosen based upon the properties that one desires from
the composition. For example, in one embodiment the composition may
include an aggressive cleansing or skin preparation ingredient.
Such active agents cleanse the surface of the skin immediately upon
application of the composition to the skin, and cleanse the skin
sufficiently before a film is formed from the first film forming
component, and before the first film forming component excludes the
active agents from the surface of the skin.
[0057] Cleansing ingredients may be capable of removing microbials,
viruses, and other foreign contaminants from the surface of the
skin. Cleansing ingredients may also be capable of scouring dead
and dying layers of skin from the skin surface. The cleansing
ingredient may suitably comprise non-ionic surfactants because:(1)
this class of compounds readily cleanses the skin, and removes the
fatty dead, and dying layers of the outer surface of the skin (the
stratum disjunction and stratum corneum); (2) this class of
compounds is typically very soluble in the water base of the
composition; (3) this type of compound is an effective antiviral
compound; and (4) this class of compounds allows the proper
functioning of the other active ingredients of the composition.
[0058] Surfactants are particularly suitable because of their
ability to cleanse at the interface of the liquid composition and
the outer layers of the skin. A particularly suitable nonionic
surfactant is sold under the trade mark Triton X-100, and comprises
octoxylenol, most suitably having 9-10 repeating units of
ethoxylation. Another particularly suitable nonionic surfactant is
nonoxynol-9, which can be used alone or in combination with other
surfactants.
[0059] Suitable antimicrobial and cleaning active agents that can
be incorporated into the composition include propylene glycol,
berberine sulfate, various quaternary ammonium compounds, such as
dimethyl benzethonium chloride, benzalkonium chloride, benzoxonium
chloride, and cetyl pyridinium chloride. Additional antimicrobial
and cleansing agents include, but not limited to
parachlorometaxylenol, nonoxynol-9, chlorohexadine gluconate, and
lauricidin (glycerol monolaurate). Other active agents include skin
healing emollient ingredients such as allantoin, aloe, dimethyl
sulfone, dimethicone, fragrances and anti-oxidants.
[0060] It is also possible to include active agents with medicinal
properties in the composition which, when delivered topically, are
absorbed by the skin and metabolized. Any active agent that is fat
soluble, or which can be rendered fat soluble, is a suitable
candidate for delivery through the compositions of the present
invention, because such agents are capable of migrating through the
final film formed by the composition, and thereafter being
topically delivered to the skin.
[0061] The medicinally active agents of the invention can be added
singly, or in any combination. Each medicinally active agent
typically comprises from about 0.01 weight % to about 3.0 weight
percent of the composition, although active agents can be present,
either singly or in combination, in quantities as high as 25 wt. %,
20 wt. %, 15 wt. %, 10 wt. %, or 5 wt. %. Most medicinally active
agents are preferably present from about 0.01 weight % to about 1.0
weight percent. Preferred medicinally active agents include
alkylglycerols, alkoxyglycerols, polyunsaturated fatty acids or
polyunsaturated oils, fat soluble vitamins, sulfur compounds,
minerals, antioxidants, amino acids, energy stimulators, steroidal
hormones, or glycoprotein hormones. Preferred medicinally active
agents also include a variety of other healing agents including
glycyrrhizic acid, ribonucleic acids, aloe vera, allantoin,
bioperine, berberine hydrochloride, colostrum, dexpanthenol,
glucosamine salts, inositol, phytantriol, pyrolidine carboxylic
acid, jojoba oil, symphytum officinal, polysorbate 80, vanilla
extract, and adducts of a nitrogenous organic base and a fatty
acid. Adducts of nitrogenous organic bases and fatty acids are
especially appropriate for use in higher concentrations.
[0062] Glycerides, including mono-, di-, and triglycerides, and
alkoxyglycerols and alkylglycerols, are particularly suitable as
active agents, or as carriers for active agents, in topical
applications. These components have independent medicinal
properties, are capable of independently migrating through the
film, and can also solubilize other fat soluble active agents and
carry them through the first film to the surface of the skin.
Particularly suitable glycerides typically comprise from about 10
to about 36 carbon atoms, can be conjugated or saturated, and are
generally liquid at room temperature. Preferred glycerides include,
lauricidin, vitamin D suspended in palm oil, conjugated linoleic
acid ("CLA"), gamma linolenic acid ("GLA"), and eicosapentaenoic
acid (EPA). Highly unsaturated oils are also especially suitable
active agents in such topical applications because such oils have
an antioxidant benefit when applied to the skin, and in addition
they are effective transport vehicles for fat soluble active
agents.
[0063] The polyunsaturated fatty acids used as medicinally active
agents include conjugated linolenic acid, alpha-linolenic acid,
alpha-linoleic acid, gamma linolenic acid, dihomo-gamma-linolenic
acid, docosahexaenoic acid, eicosapentaenoic acid. The
polyunsatured fatty oils useful in the invention include neem oil,
shark liver oil, lemon oil, or squalene. Other fatty oils include
lemon oil and squalane. Shark liver oil and/or neem oil are
typically used at higher concentrations than other medicinally
active agents, and are thus typically present at concentrations of
up to 10, 5, or 3 wt. % of the composition.
[0064] Preferred fat soluble vitamins include vitamin A, vitamin D,
vitamin E, vitamin K, a tocotrienol, lycopene, b-carotene, ascorbyl
palmitate, and luteine. Preferred sulfur compounds include
dimethylsulfone, zinc sulfate, or lipoic acid. Preferred minerals
include zinc sulfate; zinc 1-monomethionine; and compounds of
copper, calcium, magnesium, chromium, selenium, vanadium, cobalt,
and silica. Compounds include salts and chelates, among others, and
especially include calcium proprionate; copper porphyrin compounds,
silicic acid or silica gel, and copper-curcumin.
[0065] Preferred anti-oxidants include ascorbyl palmitate, neem
oil, squalene, ferulic acid, lipoic acid, grape seed extract,
boswellin, lycopene and bilberry extract. Preferred amino acids
include arginine, proline, glutamine, glycine, or trimethyl
glycine, omithine alpha-ketoglutarate, and 1-pyrroglutamic
acid.
[0066] Energy stimulators are defined as compounds that provide
easily metabolized sources of energy for the synthesis of ATP, and
include bee pollen, natural honey, forskholin, and arginine.
Preferred steroid hormones include cortisol, pregnenolone, and
dehydroepiandrosterone.
[0067] Another class of active agents include optically flourescent
or phosphorescent compounds or compositions that can absorb
ultraviolet light and re-emit it as visible light. When hands or
other skin surfaces that have been treated with the resulting
flourescent or phosphorescent compositions, exposure to a source of
ultra-violet ("black") light can be used as a method to check for
the presence of the composition on the skin. This property might be
particularly useful in skin cleaning and/or skin protecting
compositions utilized in hospital, food manufacturing, or food
service facilities, as a means for easily checking for the presence
of the cleaning or skin protecting composition.
[0068] When the composition is used to deliver medicinal active
agents, the composition may preferably be modified by the addition
of a suitable partitioning agent. Such partitioning agents
preferably comprise from about 0.1 to about 3.0 wt. % of the
composition, and even more preferably comprise from about 0.3 to
about 1.5 wt. % of the composition. Partitioning agents can be
incorporated in the composition in order to (1) facilitate the
migration of active agents through the film, and (2) modulate the
skin surface to facilitate penetration of the skin by the active
agents. Suitable partitioning agents include carbomers,
hydroxymethylcellulose, and glyceridyl monooleate, as taught, for
example, by Ogiso et al., in J. Pharm. Sci. 84:482-488 (1995), by
Roy et al., in Int'l Jnl of Pharm. 110:137-145 (1994), and by Niazy
et al., in AAPS 9th Ann. Mtg. Abst. 7080. Pharm Res. 11:5194
(1994), the disclosure from the above references being hereby
incorporated by reference.
[0069] A particularly effective class of partitioning agents for
use with the compositions of the present invention are the nonionic
polyethoxylated fatty ethers and alcohols. The molecular weight of
these agents, and their limited solubility in the liquid carrier,
cause them to form a layer on the surface of the skin even before
the first film forming component forms a film. After the film has
formed, it is believed that these agents interact with the cationic
surfactants that are anchored to the film in a manner that
facilitates the transmission of active agents from the film into
the skin. Moreover, the ethoxylation of the compounds appears to
minimize and prevent undue irritation of the skin by these
surfactant compounds. The degree of ethoxylation also appears to
affect the rate at which active agents are partitioned by the
partitioning agent.
[0070] The effectiveness of the partitioning agent at facilitating
the transmission of an active agent varies depending upon the size
and polarity of the active agent. In general, the size of the
active agent and the size of the partitioning agent are directly
related, so that larger active agents require larger partitioning
agents. The degree of ethoxylation of the partitioning agent is
also directly related to the size of the active agent and the
polarity of the active agent.
[0071] The degree of ethoxylation of the partitioning agent
typically ranges from about 10 to about 400 units of ethoxylation,
although it preferably ranges from about 10 to about 100 units of
ethoxylation, and most preferably ranges from about 10 to about 20
units of ethoxylation. The size of the partitioning agent typically
ranges from about 12 to about 36 carbon atoms, and preferably
ranges from about 12 to about 18 carbon atoms. Particularly
suitable partitioning agents include polyoxy(10) O-ethanol and ceto
stearyl alcohol.
[0072] The composition may also comprise one or more anionic
surfactants having one or more fatty moieties that are soluble in
the first film forming component. The fatty acids that comprise the
first film forming component are typically neutralized during
preparation of the composition, and are especially suitable anionic
surfactants. These surfactants are believed to be capable of
forming a substantially discreet layer in the dried structure on
the skin. Due to the unique structures of these anionic
surfactants, they are capable of anchoring in the film through
their fatty moieties, with their anionic portion being typically
oriented on the opposite side of the film from the skin (because
the anionic charge is repelled by the anionically charged skin
surface). Because the anionic surfactant is located on the exposed
side of the film, and is anchored in the film through its fatty
moieties, the surfactant imparts continuing properties to the film.
In a preferred embodiment the fatty moieties of the anionic
surfactant comprise from about 12 to about 22 carbon atoms. A
preferred anionic surfactant is a salt of stearic acid or sodium
lauryl sulfate.
[0073] In another embodiment the composition comprises a
nitrogenous organic base. The base stabilizes the emulsion when the
composition comprises an emulsion, although how such stabilization
is achieved is not well understood. The base is preferably
triethanolamine, tromethamine, or a tris amino alcohol compound
such as tris(hydroxymethyl)aminomethane,
tris(hydroxymethyl)aminoethane, with triethanolamine and
tromethamine being especially preferred. The nitrogenous base
preferably forms an adduct with the fatty acid in the first film
forming component. In a preferred embodiment the first film forming
component is modified with a fatty acid/nitrogenous base adduct
formed by mixing the fatty acid with one or more nitrogenous bases
at temperatures between about 57 and about 80 C. Such adduct, in
combination with the cationic surfactant, make at least one side of
the first film essentially lipophilic and positively charged, and
thereby attracted by the negatively charged skin.
[0074] Other ingredients may be included in the composition. Tetra
sodium EDTA, for example, is preferably added to the composition in
order to partially neutralize an emulsion of the composition. EDTA
may also sequester any hard components of the water and further
reduce the potential for any negative interactions between the hard
components of the water and the active ingredients of the
composition. From about 0 to about 0.5 parts by weight of EDTA are
typically employed. A thickener can also be added to the
composition in order to increase its viscosity, and obtain a creme
product suitable for applying and rubbing into skin. Particularly
suitable thickening agents include carboxypolymethylene (carbopol)
and sodium carboxymethyl cellulose, present in the composition at
from about 0 to about 0.6 parts by weight. Other ingredients that
can be included in the composition include process aids such as
glycerin and propylene glycol, emulsion stabilizers for the stearic
acid such as cetyl alcohol, and preservatives such as
chlorohexadine gluconate.
[0075] Additional ingredients can be added to the composition to
build upon the layering effect of the composition, and to provide
additional properties to the composition. In particular, in order
to improve the residual properties of the composition, an outer
film-forming component can be added to the composition. The outer
film-forming component can be comprised of ingredients that form a
substantially discreet film after the hydrophobic first film has
formed, and therefore which surrounds the hydrophobic film. If
properly formulated, the outer film traps and encapsulates active
agents that may be contained in the composition.
[0076] Although other film-forming ingredients will be apparent to
workers skilled in the art, a particularly suitable outer film
forming ingredient is polyvinyl pyrrolidine (PVP), because it is
initially soluble in water, but becomes insoluble upon drying and
forming a film. It is believed that PVP, which can be added to the
composition as a waxy non-soluble phase, coalesces and forms an
outer film after the hydrophobic film has formed. It is believed
that the outer film forms after the hydrophobic film has formed
because the hydrophobic film forming ingredients respond more
quickly to the evaporation of water from the composition and the
resultant concentration of non-water ingredients in the
composition. In essence, the hydrophobic film components are less
soluble than the outer film ingredients and therefore precipitate
first as water from the composition evaporates. Some of the active
agents become entrapped between the hydrophobic film and the PVP
outer film, it is further believed, because these active agents
effectively precipitate from solution after the hydrophobic film
has formed but before the outer film has coalesced. Because
nonionic surfactants are the most soluble component of the
composition, the outer film probably coalesces before the non-ionic
surfactants precipitate from solution, and the outer film probably
excludes and expels any non-ionic surfactants further from the
skin, where they can provide desired residual effects.
[0077] It is believed that the composition of the invention forms
one or more substantially discreet layers when applied to the skin.
For example, the composition typically comprises a first
hydrophobic film and a second outer film. Another layer can be
present between these two layers that comprises active ingredients.
For example, a layer of anionic moieties (from the fatty anionic
surfactants) will typically coat the surface of the first
hydrophobic film opposite the skin. Other active agents that
precipitate from the composition before the second film forms can
also form a layer between the first and outer films. Moreover, when
the second film forms it can exclude other active agents that are
still solubilized in the liquid carrier, and thereby form an
additional layer on the outside of the outer film.
[0078] These layers will typically be substantially discreet. In
many instances, however, various components of the composition will
separate into different layers of the composition. This can happen,
for example, if some of the ingredients that comprise the first
film forming component are not incorporated in the film, or if some
of the cationic surfactant does not end up between the first film
and the skin.
[0079] In some compositions the separation of ingredients among
layers can be done by design. This is especially true of
compositions used to deliver medicinal agents to the surface of the
skin. In such compositions the medicinal agent will preferably be
at least partially soluble in the first film. Some compositions
may, however, comprise more medicinal agent in the composition than
can be solubilized by the film, and as a result the medicinal agent
may separate among the layers of the composition.
[0080] Thus, the first film that eventually forms from the first
film forming component can incorporate in its structure various of
the other ingredients contained in the composition. Active agents,
in particular, are often incorporated into the film in order to
enhance the effectiveness of the active agent.
[0081] The compositions of the invention preferably are about
neutral, and even more preferably slightly basic, with pH typically
not exceeding about 8.5, 8.0, 7.8, or 7.5, and typically not below
about 7.1 or 7.5. For example, compositions having a pH of from
about 6.5 to about 8.0 are preferred. Compositions having a pH of
from about 7.1 to about 7.5 are even more preferred.
[0082] In another aspect the invention provides a phase stable
emulsion comprising one or more quaternary ammonium compounds; one
or more nonionic surfactants; one or more fatty esters; one or more
fatty alcohols; and optionally one or more highly polar compounds.
In a particularly preferred embodiment the above components are
present at a preferred ratio at the moment that the emulsion is
formed. Components that are added to the composition after the
emulsion has formed are not included in the ratio. The ratio of the
sum of the moles of quaternary ammonium compounds, surfactants, and
highly polar compounds to the sum of the moles of fatty esters and
alcohols is preferably from about 0.8 to about 1.2. In an even more
preferred embodiment the ratio is about 1.0.
[0083] Highly polar compounds that are included in the ratio
include those compounds that are ionic or that have a dipole moment
that exceeds the dipole moment of methanol. Highly polar compounds
are typically added to increase the solubility of nonpolar
compounds in polar solvents, although they can also be added as
active agents. For example, polar compounds that contain sulfur are
preferred when using the composition to treat burns because they
are a source of sulfur which is used to heal damaged skin. Highly
polar compounds include, for example, dimethyl sulfone (MSM) or
zinc sulfate.
[0084] In another aspect the invention provides a composition that
is present in the form of an emulsion comprising a fatty phase,
wherein the fatty phase comprises the one or more fatty acids
discussed above. The fatty phase further comprises one or more of
the glycerides discussed above, typically mono-, di-, or tri-, but
preferably triglycerides, alkoxyglycerols, and alkyl glycerols,
such as are in natural shark liver oil. The fatty phase optionally
comprises one or more of the other fatty components discussed above
such as the fatty esters and fatty alcohols. In a preferred
embodiment for delivering medicinal active agents to the surface of
the skin, the molar ratio of the one or more fatty acids to the one
or more glycerides and other fatty components is from about 1:2 to
about 3.5:1, even more preferably from about 1:1 to about 2.5:1,
and still even more preferably the ratio is about 2:1. It has been
found that a composition having fatty acids and glycerides within
this range of ratios are exceptional for topically delivering
active agents, and that the ratio can be varied depending upon the
topical effect desired for a particular system.
[0085] The invention also provides a process for preparing suitable
compositions. In one aspect the invention provides a process for
preparing a phase stable emulsion comprising: forming an aqueous
phase; forming a second phase comprising one or more fatty acids,
and one or more fatty alcohols and/or one or more fatty esters;
mixing the first and second phases to form an emulsion; and mixing
an organic base with the emulsion; wherein: (a) the emulsion
optionally comprises one or more quaternary ammonium compounds, one
or more surfactants, and/or highly polar compounds; and (b) the
ratio of the sum of the moles of quaternary ammonium compounds,
surfactants, and highly polar compounds, to the sum of the moles of
fatty esters and fatty alcohols is from about 0.8 to about 1.2,
preferably about 1.0. The various components are as defined above.
The emulsion is preferably formed at a temperature of from about 57
C. to about 80 C., preferably about 70 C. Moreover, the organic
base is preferably mixed with the emulsion at a temperature of from
about 57 C to about 80 C., preferably about 70 C. The fatty
ester(s) may optionally be added to the aqueous phase, although
preferably they are included in the fatty phase.
[0086] The pH of the emulsion is preferably adjusted after the
organic base is added to the emulsion to the pH levels discussed
above, preferably from about 7.1 to about 7.8. Moreover, the
emulsion can be stabilized with an emulsion stabilizer, such as a
carbomer. One or more active agents may be added to the aqueous
phase, the second fatty phase, or the emulsion, either before or
after the emulsion is formed. In particular, the loading of certain
active agents can be increased beyond a level at which an emulsion
containing that active agent would normally be stable, by adding at
least some of the active agent after the emulsion has been formed
and preferably stabilized. This active agent loading procedure can
be particularly important for providing the desired high
concentrations of active agents such as lauricidin, chlorohexidine
gluconate, dimethylsulfone, and other highly polar compounds. In a
particularly preferred embodiment some or all of the active agents
are cationic.
[0087] In another embodiment the invention provides a process for
preparing a phase stable emulsion comprising: forming an aqueous
phase; forming a second phase comprising one or more fatty acids,
one or more fatty alcohols, and one or more fatty esters; mixing
the first and second phases to form an emulsion at a temperature of
from about 57 C. to about 80 C.; and mixing an organic base with
the emulsion at a temperature of from about 57 C. to about 80 C. In
a particularly suitable embodiment the second phase comprises fatty
acids at a molar ratio of fatty acids to glycerides and other fatty
components of from about 1:2 to about 3.5:1, more preferably from
about 1:1 to about 2.5:1, and most preferably about 2:1.
[0088] The compositions of this invention can also be characterized
by the proportion of several components that are present in some of
the most preferred formulations, including wax, propolis, fatty
acids, fatty alcohols, glycerides, and quaternary ammonium
compounds. Thus, in one embodiment, these components are present in
the following weight percentages, based on the total weight of the
composition:
[0089] 1. Wax (which includes bees wax and other fatty esters):
greater than about 0.05, or 0.1 wt. %, and/or less than about 5.0,
3.0, or 1.0 wt. %.
[0090] 2. Propolis: zero, or greater than about 0.01, 0.025, or .05
wt. %, and/or less than about 5.0, 3.0, or 1.0 wt. %.
[0091] 3. Fatty acids: greater than about 0.5, 1.0, 2.0, or 3.0 wt.
%, and/or less than about 15, 10, 8,and6wt. %.
[0092] 4. Fatty Alcohols: greater than about 0.3, 0.5, 1.0, or 1.5
wt. %, and/or less than about 10, 8, or 6 wt. %.
[0093] 5. Glycerides: greater than about 0.1, 0.5, or 0.9, and/or
less than about 10, 8, and 6 wt. %.
[0094] 6. Quaternary ammonium compounds: greater than about 0. 1,
0.25, or 1.0, and/or less than about 12.0, 8.0, or 6.0 wt. %.
[0095] In one embodiment, these components are present in the
following weight proportions:
[0096] 1. Wax (which includes bees wax and other fatty esters):
greater than about 0.1 or 0.4 parts, and less than about 2.0 or 1.0
parts.
[0097] 2. Propolis: zero, or greater than about 0.025, and/or less
than about 1.5 or 1.0 parts.
[0098] 3. Fatty acids: greater than about 1.5 or 3.0 parts, and/or
less than about 9 or 6 parts. 4. Fatty Alcohols: greater than about
0.3, 0.5, 1.0, or 1.5 wt.%, and/or less than about 10, 8, or 6 wt.
%.
[0099] 5. Glycerides: greater than about 0.1, 0.5, or 0.9, and/or
less than about 10, 8, and 6 wt. %.
[0100] Quaternary ammonium compounds: greater than about 0.1 or
1.0, and less than about 8.0 or 6.0 parts.
[0101] The foregoing weight proportions apply to the composition
before it is applied to the skin or tissue. Alternatively, because
the applied lotion or creme (after the volatile components have
evaporated) consists substantially of the foregoing components, the
applied lotion or creme can be described by the foregoing
proportions, based on the total of the foregoing ingredients
equaling 100 wt. %.
[0102] Where possible, only highly purified ingredients should be
used. For example, the fatty esters should be triple distilled when
possible. Similarly, with the naturally occurring ingredients,
unwanted compounds such as heavy metals may be removed if done so
without destroying the desired properties of the natural molecules.
Other compounds can, of course, be substituted for the specific
ingredients disclosed herein, as discussed in the preceding
paragraphs and as understood by workers skilled in the art.
[0103] In another aspect of the invention, it has been found that
under certain conditions of the above-described processes for
preparing the compositions and/or phase stable emulsions of the
invention, solid particles that can be termed fatty micro-spheres
are formed. The fatty micro-spheres are typically approximately
spherical particles having a diameter of less than about 0.2 mm,
with at least a solid outer layer comprising at least some of the
fatty components of the composition. The micro-spheres may have
semi-solid or liquid interior domains, and may be at least
partially aglomerated with other particles.. Without wishing to be
bound by theory, it is believed that the formation of the fatty
micro-spheres is related to, or derived from the partial or
complete solidification of micelles, mixed micelles, or
micelle-like structures containing surface active agents, with the
lipophilic tails of the constituent molecules oriented toward the
center and, and the polar, hydrophillic heads oriented at the
periphery.
[0104] The formation of fatty micro-spheres may occur when certain
ranges of the ratios of certain components of the compositions are
maintained during certain phases of the process for the preparation
of the compositions and/or emulsions of the invention. As described
hereinabove, phase stable emulsions that may not contain fatty
micro-spheres are formed when the ratio of the sum of the moles of
quaternary ammonium compounds, surfactants, and highly polar
compounds to the sum of the moles of fatty esters and alcohols is
between about 0.8 to about 1.2. However, the desirable fatty
micro-spheres are formed only over narrower ranges of the
above-described ratio. Normally, fatty micro-spheres may form when
the ratio is between about 0.9 to about 1.1. The ratio also effects
the residual tackiness or stickiness of the compositions and/or
emulsions, after they are applied to the skin or a wound.
Stickiness decreases as the ratio of the sum of the moles of
quaternary ammonium compounds, surfactants, and highly polar
compounds, to the sum of the moles of fatty esters and fatty
alcohols, becomes closer to 1:1. It is believed that the stickiness
results from a decrease in the quality of the spheres formed. For
example, if the ratio is greater than 1.05 or less than 0.95,
spheres may form, but there is increasing stickiness as the ratio
drifts further outside that range. More preferably, the ratio is
less than about 1.01, and greater than about 0.99. It has been
found that when the ratio is about 1.0000, almost no residual
stickiness is observed after 30 seconds of rubbing the
sphere-containing compositions onto the skin.
[0105] It is to be understood that the above-described surfactants
include both non-ionic surfactants, and the anionic surfactants
created by the neutralization of fatty acids, to give salts of
fatty carboxylates, during the processes for preparing the
compositions and/or phase stable emulsion, as described above and
below. Accordingly, it has also been found that the fatty micro
spheres form in the compositions and/or phase-stable emulsion only
within certain pH ranges. A pH above about 8.5 reduces the number
of fatty micro-spheres formed, and a minimum pH must be maintained
that is effective to complete neutralization of the fatty acids,
and form the fatty micro-spheres. A pH of about 5.5 or greater is
sufficient to assure complete neutralization of typical fatty
acids. Thus, fatty micro-sphere formation is typically favorable
over a pH range from about 5.5 to about 8.5. In preferred
embodiments, pH is from about 6.5 to about 8.0. In preferred
embodiments, pH is from about 7.0 to 7.8 during the process for
producing the fatty micro-spheres, with the result that stable,
substantially uniform fatty micro-spheres are formed.
[0106] It is also believed that the formation and quality of the
fatty micro-spheres formed is a function of the temperature at
which the neutralization of fatty acids occurs. Fatty micro-spheres
do not typically form if the neutralization is carried out at
temperatures of less than about 55.degree. C. or more than about
100.degree. C. A more preferred temperature range for the
neutralization is from about 65.degree. C. to about 90.degree. C.
and the most preferred temperature range is from 70.degree. C. to
about 85.degree. C.
[0107] While not wishing to be bound by theory, it is believed that
fatty micro-spheres form as the fatty components begin to solidity
within the micelles, mixed micelles, or micelle-like structures
formed in the compositions and/or phase-stable emulsions of the
invention, as their temperature is lowered. Those of skill in the
art will recognize that the temperature at which fatty
micro-spheres form is a complex function of the identity and
quantities of the chemical components of the compositions and/or
phase stable emulsions. In certain preferred embodiments described
herein, fatty micro-sphere formation begins at about 55.5.degree.
C., and is substantially complete at about 54.9.degree. C. Once
formed, the fatty micro-spheres are remarkably stable. Therefore
the invention relates, in one aspect, to a process for preparing a
composition or phase stable emulsion having fatty micro-spheres
therein, comprising
[0108] a. mixing in any sequence:
[0109] i. one or more active agents;
[0110] ii. a nonionic or substantially nonionic first film forming
component comprising at least one fatty ester or fatty alcohol;
[0111] iii. one or more cationic surfactants comprising a
quaternary ammonium compound that is substituted with one or more
lower alkyl moieties and one or more fatty moieties comprising from
16 to 22 carbon atoms, that are soluble in the first film forming
component;
[0112] iv. one or more fatty acids;
[0113] v. optionally one or more highly polar compounds;
[0114] vi. optionally one or more non-ionic surfactants; and
[0115] vii. a liquid carrier;
[0116] wherein the mole ratio of the sum of the fatty acids,
non-ionic surfactants, quaternary ammonium compound, and highly
polar compounds, divided by the sum of the fatty esters and fatty
alcohols is from about 0.9 to about 1.1,
[0117] b. neutralizing the fatty acids with an organic base to a pH
effective to complete neutralization of the fatty acids; and
[0118] c. cooling the neutralized composition to a temperature
effective to form a composition having at least some fatty
micro-spheres.
[0119] Optionally the compositions and/or phase stable emulsions
are agitated during the process of forming the fatty micro-spheres,
by any suitable means of agitation known to those of skill in the
art. If the process is not agitated, fatty micro-spheres typically
form, but their size distributions and quality are not as uniform
as when agitation is employed.
[0120] In certain preferred embodiments of the processes of the
invention, unexpectedly uniform and high quality fatty
micro-spheres form when the ratio the sum of the moles of
quaternary ammonium compounds, non-ionic surfactants, neutralized
fatty acids, and highly polar compounds, to the sum of the moles of
fatty esters and fatty alcohols is about 1.000, the neutralization
of the fatty acids occurs between about 70.degree. C. and about
85.degree. C., the pH is between about 7.0 to about 7.8, and
agitation is employed during the formation of the fatty
micro-spheres.
[0121] In some embodiments of the above-described process,
formation of the fatty micro-spheres produces a thickening and/or
increase in the inherent viscosity of the composition or phase
stable emulsion. Any undesirable thickening or viscosity increase
may be reduced if desired, by incorporating air or other gases into
the composition while optionally agitating.
[0122] Active agents, and/or some or all of certain ingredients can
be added before or after the formation of the fatty micro-spheres.
In certain embodiments in which the ingredients and/or active
agents are added before the formation of the fatty micro-spheres,
it is believed that the chemical ingredients and/or active agents
distribute themselves within the fatty micro-spheres and the
remaining substantially aqueous medium (the "gravy") as determined
by the chemical and physical characteristics of the ingredients
and/or active agents. When present during the formation of the
fatty micro-spheres, it is believed that the ingredients and/or
active agents distribute themselves within the interior of the
fatty micro-spheres in a substantially uniform way. The
concentration of water-soluble ingredients may be the same or
different within the fatty micro-spheres as compared to the
surrounding watery fluid, at the time of micro-sphere
formation.
[0123] In certain other embodiments of the processes of the
invention, additional ingredients and/or active agents are added
after the formation of the fatty micro-spheres. Stated
alternatively, once the fatty micro-spheres are formed and/or
solidified, additional ingredients and/or active agents can be
added to the composition. In many cases, the additional ingredients
and/or active agents may not fully penetrate or become incorporated
into the fatty micro-spheres, and may be preferentially retained in
the substantially aqueous medium surrounding the fatty
micro-spheres. This can provide a clinically important benefit,
because certain water-soluble materials and/or active agents can be
artificially concentrated in the substantially aqueous medium, as
compared to the fatty micro-spheres. As a result, when a wound site
is treated with the fatty micro-sphere containing compositions, the
wound is initially bathed with a relatively highly concentrated
aqueous dose of the additional ingredient and/or active agent,
followed by a less concentrated dose when the spheres are later
absorbed by the wound.
[0124] It is to be understood that if an additional ingredient
and/or active agent is added after the formation of the fatty
micro-spheres, the additional ingredient and/or active agent added
is not included in the above described preferred ratios (of the sum
of the moles of quaternary ammonium compounds, surfactants, and
highly polar compounds, to the sum of the moles of fatty esters and
fatty alcohols). This addition technique can be employed to produce
non-tacky, high quality micro-spheres, yet allow considerable
flexibility in the permissible overall concentration of any
potentially ratio-impacting ingredient, by permitting selective
addition of some or all of the potentially ratio-impacting
ingredient to the gravy, rather than the fatty micro-spheres. For
example, in one of the embodiments of the invention, it is desired
to add Vitamin E acetate (a fatty ester that would normally be
counted in the ratios) to a desired high level. If the total
desired quantity of Vitamin E acetate is added prior to the
formation of the fatty microspheres, the ratio is 0.9642, and a
relatively sticky product is obtained. However, if the Vitamin E
acetate is added after the formation of the fatty micro-spheres,
the Vitamin E acetate is not counted when satisfying the preferred
ratios, so that a product that is not sticky after 30 seconds of
rubbing may be produced, and yet there are no other changes in the
efficacy of the product.
[0125] In another related embodiment, an additional ingredient or
active agent having a melting temperature above room temperature,
but below the temperature of formation of fatty microspheres can be
added to a previously formed composition containing fatty
micro-spheres. When the additional ingredient or active agent
melts, a substantial thinning, or decrease in the viscosity of the
solution is observed. Nevertheless, as further cooling progresses,
the additional ingredient or active agent may crystallize, again
thickening or increasing the viscosity of the composition produced.
Moreover, the crystal size of the reformed crystals of the
additional ingredient or active agent can be manipulated. By
employing agitation during the additional cooling, the crystals of
the ingredient or active agent formed can be relatively small,
numerous, have high surface area, and therefore re-dissolve quickly
upon application. Without agitation, the crystals may become large,
have relatively limited surface area and be slow to dissolve. When
said crystals are an active agent, the dissolution rate of the
large crystals formed can be reduced to provide controlled release
of the active agent.
[0126] For example, spheres may be substantially completely formed
in one of the inventive phase stable emulsion compositions at
54.9.degree. C. A blue dye is added and the background color of the
"spheres and gravy" composition is the color of mustard. Then
povidone iodine (an anti-septic active agent having a deep rust
color) is added. The povidone iodine melts and causes the apparent
viscosity of the composition to decrease, and become thoroughly
mixed. The resulting mixture is the color of pea soup. The mixture
is allowed to cool to room temperature over at least about 4 hours,
(preferably at least about 24 hours, more preferably at least about
48 hours). Optionally, the cooling takes place in a substantially
sealed vessel. Cooling in an unagitated substantially sealed vessel
reduces the rate of cooling and makes larger, more uniform povidone
iodide crystals. After cooling, the product is agitated by
incorporation of air for three minutes, such that the specific
gravity is reduced from about 0.98 to about 0.91. This mix is now a
lemon-lime green with rust colored speckles. With additional aging,
the rust colored speckles disappear. Under a microscope, the
reformed povidone iodine crystals are coated with green "gravy",
obscuring their true color. Upon application of the anti-septic
composition, the intentionally large and slow-to-dissolve povidone
iodide crystals release iodine active agent over an extended period
of time of up to three to four hours, extending the duration of
anti-septic efficacy.
[0127] In another example, Triclosan is an anti-septic active agent
reported to melt above the temperature of fatty micro-sphere
formation. Surprisingly, the Triclosan appears to melt or dissolve
at temperatures below the sphere formation temperature. After about
one minute of mixing, the viscosity of the mixture suddenly drops
and turns the color of mustard. The melt is allowed to cool to room
temperature over at least 4 hours. Cooling in an unagitated
substantially sealed vessel reduces the rate of cooling and results
in larger, more uniform crystals. After cooling, the product is
agitated by incorporation of air for three minutes, such that the
specific gravity is reduced and has a bright yellow color. Upon
application of the anti-septic composition, the large and
slow-to-dissolve crystals meter Triclosan active agent to the skin
over an extended period of time, extending the duration of
anti-septic efficacy.
[0128] In yet another embodiment of the above described process,
additional ingredients, optically fluorescent or phosphorescent
compounds, and/or other active agents may be mixed with the
composition or phase stable emulsion after the formation of the
microspheres. Preferably, the additional ingredients and/or active
agents are melted or dissolved into the composition or phase stable
emulsion, to form a modified composition containing fatty
micro-spheres, then the resulting modified composition is further
cooled to at least partially crystallize the additional ingredient
and/or active agent. Optionally, the modified composition may be
agitated or it's cooling rate controlled so as to modify the
crystal size of the additional ingredient and/or active agent.
[0129] In some embodiments of the applications of the instant
compositions, at least two different compositions within the scope
of the invention are separately applied to the same area of the
skin or body, to form a layered coating on the body. For example,
in one embodiment, a composition according to the invention having
few or no active ingredients is first applied to the hands and
allowed to dry. The resulting substantially dry base coat seals and
protects the skin from direct contact with potentially irritating
ingredients or active agents. In a subsequent step, a composition
within the scope of the invention having ingredients or active
agents, including those designed to form a sealing barrier film is
applied to the same, previously coated, area of the skin. Film-
forming ingredients that are effective to form such sealing barrier
films include polymeric substances such as Polyderm CO, PE and SA
(available from Akzo Chemical Co., Sayreville, N.J.) and the like.
Further layers of the compositions of the invention, containing
other active agents maybe applied if desired. The resulting
multi-layer layered coating structure on the hands is non
irritating and impervious to aggressive industrial chemicals such
as paint, solvents acids and the like. Such a multi step process is
particularly useful in protecting workers hands who work in the
petroleum, petrochemical and chemical industries.
Experimental
[0130] The following examples are put forth so as to provide those
of ordinary skill in the art with a complete disclosure and
description of how the compounds claimed herein are made and
evaluated, and are intended to be purely exemplary of the invention
and are not intended to limit the scope of what the inventors
regard as their invention. Efforts have been made to ensure
accuracy with respect to numbers (e.g., amounts, temperature, etc.)
but some errors and deviations should be accounted for. Unless
indicated otherwise, parts are parts per 100 parts total weight of
the final composition, which is equivalent to weight percent of the
final composition, temperature is in .degree. C. or is at room
temperature, and pressure is at or near atmospheric. Listed
compounds are commercial grade.
EXAMPLE 1
[0131] An aqueous phase was first prepared by mixing the following
components in the weight proportions listed. The aqueous phase was
heated to 70 C and mixed until creamy and uniform.
1 NAME OF INGREDIENT WEIGHT % DI. water 63.14 Merquat 550
Polyquaternium-7 1.150 Dimethyl Distearyl Ammonium Chloride 1.300
Berberine Hydrochloride 0.013 Active Agents 4.75
[0132] A fatty phase was next prepared by mixing the following
components in the weight proportions listed, and heating the
mixture to 70 C. 0.500 weight % lemon oil were then added to the
mixture. The fatty phase thus formed was then added to the aqueous
phase, and mixed until uniformly consistent. Temperature was
maintained at 70 C.
2 NAME OF INGREDIENT WEIGHT % Stearic Acid 3.750 Cetyl Alcohol
2.955 Lauricidin 3.150 Propolis 0.400 Crude Bees Wax 1.000 Other
Active Agents 3.450
[0133] A third mixture was then prepared by combining the following
ingredients at the weight proportions listed, at ambient
temperature. The third mixture was then combined with the above
mixture under high shear agitation to form an emulsion, with the
temperature maintained at 70 C.
3 NAME OF INGREDIENT WEIGHT % D.I. Water 3.000 TEA 1.540 Tetra Na
EDTA (solid) 0.300
[0134] The emulsion was allowed to cool to 50 C., and 4.53 weight %
of processing aids were mixed with the emulsion. 2.5 weight % of
other active agents were then added to the emulsion (including 0.25
% chlorohexidine gluconate), and the pH was lowered to about 7.4
with citric acid.
EXAMPLE 2
[0135] An emulsion was formed substantially following the procedure
of Example 1. The aqueous phase contained:
4 NAME OF INGREDIENT WEIGHT % Water 65.01 Dimethyl Sulfone 0.830
Dimethyl Distearyl Ammonium Chloride 4.500 Active Agents 3.683
[0136] The fatty phase contained:
5 NAME OF INGREDIENT WEIGHT % Stearic Acid 4.421 Cetyl Alcohol
4.119 Crude Bees Wax 0.900 Propolis 0.750 Lauricidin 3.840
Glycerides 3.993 Cetyl Lactate 0.250 Ascorbyl Palmitate 0.150
Active Agents 0.575
[0137] 4.66 weight % of processing aids were added to the mixture.
2.319 weight % of triethanolamine were then added to the mixture to
adjust the pH to 6.9.
EXAMPLE 3
[0138] This example illustrates the preparation of an emulsion
suitable for application to children's skin. An emulsion was formed
substantially following the procedure of Example 1. The aqueous
phase contained:
6 NAME OF INGREDIENT WEIGHT % D.I. Water 80.29 Berberine
hydrochloride 0.05 Dimethyl Distearyl Ammonium Chloride 0.25 Active
Agents 0.35 The fatty phase contained: Stearic Acid 3.0 Cetyl
Alcohol 1.7 Crude Bees Wax 0.5 Propolis 0.1 Lauricidin 0.98
Ascorbyl Palmitate 0.2 Active Agents 0.15
[0139] The quantity of lauricidin added to the fatty phase was
sufficient to balance the critical mole ratios for the formation
and stability of the emulsion. 7.85 weight % of processing aids,
(including a carbomer and propylene glycol) were added to the
mixture. 1.35 weight % of triethanolamine were then added to the
mixture to form the emulsion and adjust the pH to 7.1, to enhance
the protection of tender young skin.
[0140] Additional lauricidin (3.15 weight %) was added after the
emulsion was formed and stable, to provide the safe and non-toxic
anti-microbial activity needed, but not disrupt the phase stability
of the emulsion.
EXAMPLE 4
[0141] This example illustrates the preparation of an emulsion
suitable for application to children's skin. An emulsion was formed
substantially following the procedure of Example 1. The aqueous
phase contained:
7 NAME OF INGREDIENT WEIGHT % D.I. Water 80.29 Berberine
hydrochloride 0.02 Dimethyl Distearyl Ammonium Chloride 0.1 Active
Agents 0.35 The fatty phase contained: Stearic Acid 3.0 Cetyl
Alcohol 1.7 Crude Bees Wax 0.4 Propolis 0.1 Lauricidin 0.895
Glycerides 0.65 Ascorbyl Palmitate 0.2 Active Agents 0.15
[0142] The quantity of lauricidin added to the fatty phase was
sufficient to balance the critical mole ratios for the formation
and stability of the emulsion. 6.60 weight % of processing aids
(including a carbomer and propylene glycol) were added to the
mixture. 1.25 weight % of triethanolamine and 0.1 weight % of
tetra-sodium EDTA were then added to the mixture to form the
emulsion and adjust the pH to 6.8, to enhance the protection of
tender young skin.
[0143] Additional lauricidin (3.485 weight %) was added after the
emulsion is formed and stable, to provide the safe and non-toxic
anti-microbial activity needed, but not disrupt the phase stability
of the emulsion.
EXAMPLE 5
[0144] An emulsion was formed according to Example 1, except that
chlorohexidine gluconate (CHG) was added at 0.69 weight % (on an
active basis, using a 20% aqueous solution of CHG). The subsequent
emulsion was low in viscosity, and caused a perception of an
unpleasant rush of blood to the hands. Users feared their hands
would be hurt with continued use.
[0145] Accordingly, in an improved procedure, the Example 1
emulsion was prepared (except for a lowering of water, to
compensate for water to be added later with the CHG), but the 0.69
weight % of CHG was added after the emulsion was stable and cooled
to 50.degree. C. The emulsion prepared by the improved procedure
had good viscosity, and eliminated the perception of blood rush to
the hands.
EXAMPLE 6
[0146] This example illustrates the preparation of a neutral
emulsion having only a small quantity of active agents and
non-ionic surfactants, suitable for application to damaged,
irritated or bleeding skin. Such emulsions are typically applied as
a base coat on damaged skin prior to applying an emulsion having
potentially irritating agents, such as the CHG in the emulsion of
Example 1. An emulsion was formed substantially following the
procedure of Example 1. The aqueous phase contained:
8 NAME OF INGREDIENT WEIGHT % D.I. Water 64.47 Dimethyl Distearyl
Ammonium Chloride 4.50 Dimethylsulfone 0.636 Active Agents 0.60 The
fatty phase contained: Stearic Acid 3.91 Ceryl Alcohol 3.50
Lauricidin 4.00 Glycerides 3.422 Active Agents 0.15
[0147] 11.36 weight % of processing aids were added to the mixture
(including a carbomer stabilizer and propylene glycol). 3.1 weight
% of triethanolamine and 0.1 weight % of tetra-sodium EDTA was then
added to the mixture to form the emulsion and adjust the pH to
7.1.
EXAMPLE 7
[0148] This example illustrates the preparation of a composition
for removing warts. An emulsion was formed substantially following
the procedure of Example 1. The aqueous phase contained:
9 NAME OF INGREDIENT WEIGHT % D.I. Water 58.23 Dimethyl Distearyl
Ammonium Chloride 2.50 Dimethylsulfone 1.0 Merquat 550 1.15
Berberine Hydrochloride 0.30 Zinc Sulfate 0.20 Arabino Galactan
0.25 Triton X-100 1.0 Nonoxynol-9 1.0 Pyrolidine Carboxylic Acid
0.2 Poly oxy 10 2.0 Aloe Vera 0.25 The fatty phase contained:
Stearic Acid 4.1 Cetyl Alcohol 3.82 Lauricidin 3.80 Crude Bees Wax
0.4 Propolis 0.2 Allantoin 0.3 Lemon Oil 0.8 Vitamin E Acetate 0.4
Ascorbyl Palmitate 0.2 Glyceryl decanoate 0.5 Neem Oil 0.758 Shark
Liver Oil 2.50 Eicosapentaenoic Acid 0.36 Conjugated Linoleic Acid
0.36 Gamma Linolenic Acid 0.36 Tetra Na EDTA 0.3 Triethanolamine
1.724 Carbomer 940 NF 0.12 Propylene Glycol 3.5
[0149] A third mixture of 3 weight % water, 1.724 weight %
triethanolamine, and 0.3 weight % tetra-sodium ethylene diamine
tetraacetic acid was formed, then mixed with the aqueous and fatty
phases at 70.degree. C. to form the emulsion. The emulsion was
cooled to 55.degree. C., and mixture of 3.5 weight % water, 0.12
weight % Carbomer 940 NF, 3.5 weight % propylene glycol, and 0.755
weight % of the dimethylsulfone, were added to the emulsion. The
emulsion was cooled to 50.degree. C., and 0.1 weight % of
Boswellin, 0.3 weight % of NDHA, 0.3 weight % of Tomatine, 0.01
weight % Vitamin A, 0.1 weight % of Vitamin D, and 0.2 weight % of
Lycopene were mixed with the emulsion.
EXAMPLE 8
[0150] This example illustrates the preparation of a composition
for treating bums. An emulsion was formed substantially following
the procedure of Example 1. The aqueous phase contained:
10 NAME OF INGREDIENT WEIGHT % D.I. Water 59.825 Dimethyl Distearyl
Ammonium Chloride 4.7 Dimethylsulfone 0.83 Merquat 550 1.15
Triton-X-100 0.0 Tomatine 0.30 Boswellin 0.10 Arabino Galactan 0.25
Active Agents 2.79 The fatty phase contained: Stearic Acid 4.1
Cetyl Alcohol 3.82 Lauricidin 4.00 Crude Bees Wax 0.9 Propolis 0.3
Other Active Agents 5.203
[0151] A third mixture of 3 weight % water, 1.577 weight %
triethanolamine, and 0.4 weight % tetra-sodium ethylene diamine
tetraacetic acid was formed, then mixed with the aqueous and fatty
phases to form the emulsion. A mixture of 3.0 weight % de-ionized
water, 4.42 weight % process aids (including a carbomer
stabilizer), 0.21 weight % dimethylsulfone, and 0.275 weight % of
Active ingredients were then mixed with the emulsion.
EXAMPLE 9
[0152] This example illustrates the preparation of another
composition for treating bums. An emulsion was formed substantially
following the procedure of Example 1. The aqueous phase
contained:
11 NAME OF INGREDIENT WEIGHT % D.I. Water 50.068 Dimethyl Distearyl
Ammonium Chloride 4.7 Dimethylsulfone 0.597 Active Agents 3.44 The
fatty phase contained: Stearic Acid 4.1 Cetyl Alcohol 3.82
Lauricidin 3 Squalene 0.6 Ascorbyl Palmitate 0.26 Other Surfactants
0.6 Other Active Agents 5.385
[0153] The aqueous and fatty phases were mixed, then a third
mixture of 3 weight % water, 1.577 weight % triethanolamine, and
0.4 weight % tetra-sodium ethylene diamine tetraacetic acid was
added to the aqueous and fatty phases at 70.degree. C. to form the
emulsion. The emulsion was cooled to 55.degree. C., and 3.0 weight
% de-ionized water, 8.92 weight % process aids (including a
carbomer and propylene glycol), 0.403 weight % dimethylsulfone, and
5.86 weight % of Active ingredients was mixed with the emulsion.
The emulsion was then cooled to 50.degree. C., and then another 0.4
weight % of active ingredients were added to the stabilized
emulsion.
EXAMPLES 10-14
[0154] These examples illustrate compositions for treating bums and
skin lesions. The emulsions were formed substantially following the
procedures described above. The final compositions contained:
12 Example # 10 11 12 13 14 Application of Deep Surface Thermal
Radiation Deep Composition Wounds Wounds Burns Burns Wounds Name of
Ingredient Wt % Wt % Wt % Wt % Wt % Water 60.364 70.06 67.67 70.796
63.25 Dimethyl Distearyl 4.5 4.5 4.5 4.5 4.5 Ammonium Chloride Aloe
Vera 0.250 0.100 0.250 0.400 0.300 Allantoin 0.600 0.150 0.500
0.300 0.300 Ferulic Acid 0.080 0.050 0.080 0.100 Dimethylsulfone
0.817 0.700 0.761 0.830 0.647 (Pre-emulsion) Pyrolidine Carboxylic
0.200 0.200 0.100 0.200 0.200 Acid Dimethyl Benze- 0.250 0.500
0.250 0.250 0.250 thonium Chloride Colostrum 0.200 0.200 0.200
0.300 0.300 Lipoic Acid 0.050 0.050 0.080 0.080 0.080 Bilberry
0.200 Grape Seed Extract 0.100 0.200 0.200 0.400 0.300 Zinc
Methionone 0.200 0.100 0.200 0.200 Zinc Sulfate 0.100 0.200 0.100
0.200 0.200 Silica Gel 0.100 0.100 0.050 0.100 0.100 Bioperine
0.080 0.080 0.080 0.080 0.080 Arginine 0.300 0.250 0.250 0.300
0.300 Proline 0.100 0.100 0.100 0.100 0.100 L-Glutamine 0.100 0.100
0.100 0.400 Trimethyl Glycine 0.100 Glycine 0.100 Cu-Curcumin 0.100
0.100 0.050 Glycyrrhizic Acid 0.050 0.050 Glucosamine HCI 0.100
0.100 Natural Honey 0.200 RNA 0.100 0.100 Inositol 0.200 Boswellin
0.150 Berberine HCI 0.050 Dexpanthenol 0.330 0.330 0.630 0.330
0.330 Phytantriol 0.110 0.110 0.315 0.110 0.110 Tetra Sodium EDTA
1.250 0.750 1.250 Polysorbate-80 .200 0.100 0.300 0.040 Symphytum
0.025 Stearic Acid 4.100 4.128 4.100 4.100 4.100 Cetyl Alcohol
3.820 3.820 3.820 3.820 3.820 Crude Beeswax 0.900 0.900 0.900 0.600
0.600 Lauricidin 3.800 3.700 4.000 4.000 3.800 B-Carotene - 95%
0.016 Ascorbyl Palmitate 0.200 0.150 0.150 0.200 0.200 Neem Oil
0.300 0.300 0.400 0.495 0.514 Shark Oil 2.310 2.000 1.592 3.300
2.000 Conujugated Linoleic 0.400 0.400 0.484 0.315 0.400 Acid
Eicosapentaenoic Acid 0.500 0.500 0.484 0.315 0.500 Lemon Oil 0.200
0.400 0.200 0.200 0.200 Pregnenolone 0.200 0.200 0.200 Dihomo Gamma
0.100 0.100 0.100 0.100 0.100 Linolenic Acid Cetyl Lactate 0.250
0.250 Gamma Linolenic 0.400 0.400 0.484 0.315 0.400 Acid B-Carotene
- 95% 0.016 0.002 0.0160 0.188 0.002 Propolis 0.200 0.300 0.300
0.025 0.025 Water 0.000 0.00 Triethanolamine 12.400 5.163 5.500
5.400 Propylene Glycol 4.000 3.500 4.000 4.000 4.000 Water 0.000
0.00 2.000 Carbomer 980 NF 0.500 0.500 0.500 0.500 Carbomer 940 NF
0.080 Glycerin 0.300 0.300 0.300 0.300 0.300 Vitamin A 0.002 0.002
0.002 0.002 0.002 Vitamin D 0.002 0.002 0.002 0.002 0.002 Vitamin K
0.002 0.002 0.002 0.002 0.002 Vitamin E 0.150 0.150 0.150 0.250
0.250 B-Carotene - 95% 0.188 0.011 Vanilla Extract 0.050 0.060
0.050 0.050 0.050 Tocotrienol 0.080 0.080 0.080 0.080 0.080
Pregnenolone 0.200 0.200 Lycopene 0.100 0.100 0.300 0.100
Dimethylsulfone (Post 0.239 Emulsion) Tetra Na EDTA 0.400 0.400
Water 1.750 Triethanolamine to 1.577 give pH 6.9 .+-. .1
EXAMPLE 15
[0155] A product having the composition of Example 10 was used to
treat a wound on a patient's heel that had resisted healing for
over six weeks. Two to three times per day the open wound was
packed with the product and covered with gauze. The length, width,
and depth of the wound were measured approximately weekly, and the
estimated volume of the wound was calculated and plotted versus
time, as shown in FIG. 1.
EXAMPLE 16
[0156] A nurse dropped a hot curling iron between her breasts while
dressing, causing a severe bum. The nurse subsequently applied a
product having the composition of Example 12 to the bum. Not only
did the burn heal completely, but no scar tissue was formed in this
sensitive area.
EXAMPLE 17
[0157] Radiation bums are often a byproduct of radiation treatment
of cancer. A product having the composition of Example 13 was
applied topically to the skin of predetermined site of radiation
treatment for a cancer patient before the radiation treatment. No
bum was apparent after radiation therapy, and the attending
physician described the non-event as "extraordinary".
EXAMPLE 18
[0158] The following protocol is used to prevent radiation-induced
dermatitis and related skin injury using, for example, the
composition of Example 13. Following the procedures for application
carefully will ensure successful completion of radiation therapy
without injury to the overlying skin and tissue:
[0159] 1. Apply composition to areas marked for radiation therapy.
Apply one (1) hour before radiation therapy.
[0160] 2. Reapply immediately after radiation therapy.
[0161] 3. Technique for application:
[0162] a. With a clean cotton swab or a tongue blade, apply thin
layer or coating to cover completely the marked areas for radiation
therapy;
[0163] b. Wait fifteen (15) seconds;
[0164] c. Then, with a clean fingertip, rub into skin until fully
absorbed.
EXAMPLE 19
[0165] The following protocol is used to maintain the skin in a
healthy state during and after radiation therapy and will help
prevent skin infections and other tissue damage from developing
using, for example, the composition of Example 13.
[0166] 1. Apply twice daily, on day of therapy--two (2) or four (4)
hours after last application of composition of Example 13, and at
bedtime.
[0167] 2. On off days (no radiation therapy), apply three (3) times
(morning, noon and night).
[0168] 3. Technique for application is the same as described above
for Example 18.
[0169] 4. Wait fifteen (15) seconds, then rub into skin.
EXAMPLE 20
[0170] The following protocol is used to treat first, second, and
third degree burns, using, for example, the compositions of
Examples 10 & 11. Carefully following the procedures, full
application will ensure successful healing with limited scarring at
the burn site. Should any signs of localized or systemic infection
occur, then aggressive antibiotic therapy is indicated and should
be started immediately.
Initial Assessment of Burns
[0171] Emergent phase (0 to 72 hours post-burn). Clinical
assessment and complete history and physical are critical during
this phase of treatment.
[0172] 1. Rule of nines is the easiest way to assess the extent of
burn in adults.
[0173] 2. Depth of burns.
[0174] a. Partial thickness (intradermal)--these injuries may
appear red or pink, often with blister formation;
[0175] b. Full thickness--these injuries may be charred or
marble-gray in color, dry and anesthetic;
[0176] c. Partial thickness burns may also have some anesthesia at
times due to nerve endings being injured so the pain response is
useful only when positive indicating a partial thickness burn.
Directions for Use
[0177] 1. Apply to entire area of burn with some overlap onto
normal tissue to ensure that all unrecognized burned tissue is
covered (early in the course of a burn, the area of burn may be
underestimated).
[0178] 2. Apply immediately or as soon as possible to the burned
areas after estimates of percent of burn and degree of burn are
completed.
[0179] 3. Apply two (2) to three (3) times per day.
[0180] 4. Cover the treated burn with one (1) layer of flexible
gauze-like conform, etc.
[0181] 5. Debridement is not necessary, and in some embodiments may
be avoided during one or more applications, but will generally
occur with the dressing change. More extensive debridement of
blisters or eschar should be done as is clinically indicated.
[0182] 6. Continue applications until patient is healed.
EXAMPLE 21
[0183] The following protocol is useful for treating stage 1, stage
2, stage 3, or stage 4 wounds, using the composition set forth in
Example 11 (for stage 1 and stage 2 wounds) and Examples 10 and 14
(for stage 3 and stage 4 wounds). The antibiotic concentration for
stage 1 and stage 2 wounds is greater typically to allow
penetration through the epidermis and dermis and superficial
wounds.
Classifications
[0184]
13 Stage 1: Red, unbroken skin, no blanching. Stage 2: Blistered or
broken skin. Wound base moist and pink. Free of necrotic tissue.
Stage 3: Extends through the dermis to involve subcutaneous tissue.
Stage 4: Deep tissue destruction extending through subcutaneous
tissue, may involve muscle layers, joint and/or bone. Present as a
deep crater. May include necrotic tissue. Note: Any wound with
eschar cannot be properly staged and should be classified as a full
thickness wound.
Directions for Use
[0185] 1. Make all appropriate measurements of size, and dimensions
of erythema and eschar.
[0186] 2. Culture wound.
[0187] 3. Debride wound if necessary.
[0188] 4. Make accurate assessment of depth using a sterile swab
and measuring the depth from the swab.
[0189] 5. For stage 1 and stage 2 wounds, apply a thin coat of the
composition to the wound and let stand for 30 seconds. Then,
topically run the formula into the skin observing the oxidation
effect.
[0190] 6. For stage 3 and greater wounds, apply the composition
making sure to completely fill the wound, including any voids,
channels, or cavities in the tissue or walls of the wound, to
slightly above epidermal level.
[0191] 7. Cover the wound with one (1) layer of gauze bandage and
wrap with conform to keep the areas of tunneling or undermining
fully saturated and dressings intact.
[0192] 8. Change dressings two (2) or three (3) times daily,
repeating this process.
Notes
[0193] 1. It is not necessary to use any microbial cleaners during
the healing process. Irrigating with normal saline may be
appropriate.
[0194] 2. If there appears to be evidence of topical wound
infection that stays localized and does not extend greater than 0.5
to 1.0 centimeters beyond the wound margin and the patient does not
become febrile, then proceed with the application as prescribed.
The topical infection characteristically remits within 12-36 hours.
If the patent becomes febrile or if there is a question of
cellulitis, then proceed with vigorous systemic antibiotic therapy
in addition to the treatment.
[0195] 3. If significant eschar formation is present, debridement
is indicated prior to initial treatment. Characteristically, the
appropriate treatment will soften the eschar formation and gently
lift this to extrusion as part of the healing process in three (3)
to six (6) days if sharp and blunt disection is not readily
available.
[0196] It will be apparent to those skilled in the art that various
modifications and variations can be made in the present invention
without departing from the scope or spirit of the invention. Other
embodiments of the invention will be apparent to those skilled in
the art from consideration of the specification and practice of the
invention disclosed herein. It is intended that the specification
and examples be considered as exemplary only, with a true scope and
spirit of the invention being indicated by the following
claims.
* * * * *